The growing body of evidence that an endotoxemia of intestinal origin develops in a variety of major non-septic as well as septic disorders makes it necessary to develop a therapy for its elimination. An effective therapy requires more understanding of 1) the processes that facilitate the transfer of endotoxin from the gut; 2) the mechanism by which endotoxin inflicts tissue injury; and 3) the factors that govern the clearance, distribution and detoxification of endotoxin. Recent data indicate an increasingly important role for the vasoactive agents in these phenomena, and the likelihood that the platelet, which has recently been shown to be a carrier of endotoxin, can be a major source of such agents (PGE2, serotonin, acid hydrolases) because endotoxin can trigger their release from aggregated platelets. This study proposes to measure the in vivo distribution of circulating endotoxin between the plasma and the platelets, the role of the platelet in the clearance and detoxification of endotoxin, and in the vascular injury produced by endotoxin. The tissue distribution of platelets carrying endotoxin and those free of endotoxin will be determined by their attached isotopes (I131 and I125 respectively). These data will be compared with data from animals pretreated or treated with aspirin and with corticosteroids. Comparative data on the tissue injury produced by endotoxin will be obtained in animals with and without thrombocytopenia (by platelet-phoresis). Detoxification of injected endotoxin (labelled with Cr51) will be determined by the difference between the amount of Cr51 in the blood and tissues, and the fraction that is still biologically active (undetoxified) by the Limulus lysate test.